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International Journal of Bioprinting                                Progress in bioprinted ear reconstruction






 Study  Aim of study  Study   Animal   Study focus  3D printing   Components  Printed  Printed  Cell nature/type  Notable post-  Assessment   Findings  Limitations and suggested
 setting  model (if   technique  shape  material  printing   of success/                      improvements
 any)                             modifications  integration
                                                             •  The PCL support was completely covered by
                                                               the regenerated cartilage with satisfactory
                                                               integration.
                                                             •  Tissue-engineered cartilage shows typical
                                                               phenotype of mature elastic cartilage similar
                                                               to microtia ear tissue with typical lacuna
                                                               structures and strong positive staining of
                                                               safranin O, type Il collagen, and Verhoeff-van
                                                               Gieson (EVG).
 Liao et al.    To reconstruct the auricle   In vivo   Rabbit  Indirect   Molds printed   Scaffold only  Resembling   Other:   Diced cartilage   PRP was mixed   Histopathology;  •  The porous, hollow, poly-amide auricular   The synthetic, non-
 (2019)  [24]  using a porous, hollow,   animal  printing  by SLS  pinna  PGLA   graft  with diced cartilage  mechanical   mold prepared by 3D printing and packed   biodegradable poly-amide
 3D-printed mold and   membrane   and sodium citrate,   testing  with diced cartilages and PRP graft showed   induced a cystic-like
 autologous diced cartilage       and this paste was           appropriate biomechanical properties and   reaction around the
 mixed with PRP                   inserted into the            maintained it shape, with good chondrocyte   implant. It is unclear
                                  printed porous               viability and the production of a cartilaginous  whether this translates in
                                  scaffold                     extracellular matrix           the clinical setting to the
                                                             •  It was found that mixing the cartilage   formation of a seroma or a
                                                               with a PRP improved the viability of the   chronic granuloma/foreign
                                                               diced cartilage when wrapped in a PLGA   body reaction. Another
                                                               membrane.                      limitation of this work is
                                                             •  At 4 months, the diced cartilage pieces within   that we did not explore the
                                                               the mold had fused, and the gross appearance  possibility of using other
                                                               was similar in shape to an auricle.  biodegradable materials,
                                                             •  No complications (e.g., hematoma, seroma, or  such as PLGA for the
                                                               infection) were observed at the implantation   hollow auricle mold.
                                                               site during the postoperative period.
                                                             •  The results of histological staining showed
                                                               that the diced cartilages after shaping retained
                                                               viable chondrocytes and a complete ECM,
                                                               with positive staining for GAGs, collagen
                                                               fibers, and elastic fibers, which determine the
                                                               biomechanical properties of the cartilage.
 Zhou et al.   To clinically apply tissue-  In vitro;  N/A  Indirect   A resin model was  Scaffold printed   Resembling   PGA,    Isolated microtia   Expanded microtia   Histopathology;  •  It is possible to successfully design, fabricate,   •  Small sample of only 5
 (2018)  [20]  engineered and 3D-printed  in vivo   printing  generated through  first and then   pinna  PLA, and   chondrocytes  cartilage cells were   mechanical   and re-generate patient-specific external ears   patients
 ear-shaped cartilage to   human   3D printing. This   seeded with cells  PCL were   evenly dropped   testing; electron   (in human subjects).  •  Longest follow-up of
 human subjects for the first  trial  resin ear model   processed   onto the PGA/PLA   microscopy;   •  12 weeks of tissue expansion were used to   only 2.5 years (other
 time.  was used to cast   into the ear   layer of the scaffold,  other:   create a large enough skin flap. A facial flap   cases 2–18 months):
 a pair of negative   scaffold    followed by 5-h   photography   was used to cover the back and the helix rim   unknown result after
 molds.                           incubation at 37°C,  and visual   of the engineered ear graft, which not only   complete degradation of
                                  5% CO The      inspection of   provided sufficient blood supply, but also   PCL scaffold (takes 2–4
                                       2.
                                  construct was   final clinical   protected the graft from extrusion.  years)
                                  then cultured in   result at 1, 2, 3,   •  Subsequent surgeries (scar revision) were   •  Only pilot study: further
                                  chondrogenic   6, 9, 12, 18, 24,   conducted for removing the pedicle of skin   work necessary to
                                  medium for 12   and 30 months   flap at 6 months and repairing scar at 18   translate this into routine
                                  weeks.         post-surgery to   months, which allowed for tissue biopsies of   clinical practices
                                                 record swelling,   the implanted ear framework.  •  Optimization and
                                                 inflammation   •  After two weeks, the initial postoperative   standardization in
                                                 signs, and shape   edema slowly reduced, and the shape of the   scaffold fabrication, cell
                                                 recovery.     reconstructed ear, as well as the color of the   expansion, and in vitro
                                                 MRI (1.5T) to   covered skin, gradually recovered. Within 6   cartilage engineering,
                                                 trace cartilage   months post-implantation, only the basic ear   surgical procedures are
                                                 regeneration   contour was observed, while key auricular   still required.
                                                 and PCL core   structures, such as helix, triangular fossa,   •  Single center
                                                 degradation   anti-helix, and cavum conchae, became
                                                               gradually distinct after 9 months.
                                                                                                         (Continued)


            Volume 9 Issue 6 (2023)                        301                        https://doi.org/10.36922/ijb.0898
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